Dimerization of GPCRs has been the subject of intense interest. Class C GPCRs, such as gamma-aminobutyric acid type B (GABA-B) receptors, form dimeric assemblies, essential both for trafficking of receptors to the cell surface and for ligand-induced activation of receptors and G-protein coupling, and detailed models for receptor and G-protein activation have been proposed. In contrast, no conclusion has yet been reached as to the importance of dimerization for class A receptor function; the role of receptor monomers or dimers in signal transduction is controversial. Models proposed to explain the mechanism of receptor-catalyzed G-protein activation assumed the interaction of G-protein with a receptor monomer. More recently, class A GPCRs have been described as monomers and dimers in living cells by resonance energy transfer methods. For rhodopsin, dimer particles and higher order oligomers have been visualized in disk membranes by atomic force microscopy. Based on structural constraints, a model was suggested in which a receptor dimer provides an extensive contact area for the heterotrimeric G-protein; the surface area of a GPCR monomer was deemed insufficiently large to accommodate both the G-alpha and G-beta-gamma subunits simultaneously. However, alternate models for the interaction of a monomeric rhodopsin with a G-protein heterotrimer have also been proposed. Signal transduction may well involve receptor dimers, but the molecular determinants for G-protein recognition and activation may reside in one receptor protomer. A rigorous investigation into the properties of GPCR monomers and dimers requires an experimental setup which allows the generation of well defined populations of receptor monomers or dimers. NTS1 monomers and rhodopsin monomers have been characterized in a carefully controlled, low detergent environment (excess detergent severely disrupts the receptor/G-protein interaction). In addition, defined monomers have been reported for rhodopsin and the beta-2 adrenergic receptor in a lipid environment. These studies confirmed that a monomeric GPCR is the minimal entity necessary for signaling, as was already concluded from studies with rhodopsin more than 30 years ago. Defined receptor dimers are technically more difficult to obtain. Our work on NTS1 is currently one of only two such studies performed in detergent solution. Existing reports on rhodopsin dimers in lipid disks acknowledge the possibility of mixtures of parallel and anti-parallel receptor dimers. The rates of transducin (G-protein) activation by rhodopsin have been reported to be lower in detergent compared to a lipid environment; this may be attributable to a faster docking process to the membrane surface and a more precise orientation of the G-protein on the receptor. Currently, there is no comprehensive study of one particular GPCR in defined monomer or dimer form in both a detergent and lipid environment. Our detergent/lipid comparison for NTS1 will for the first time give a complete view of the pharmacological properties of one receptor in two different environments. In addition, we investigate the influence of the lipid type on NTS1 signaling.